This invention relates generally to the field of drug delivery, and in particular to the pulmonary delivery of powdered medicaments. More specifically, the invention relates to techniques for forming openings in receptacles to facilitate extraction of powdered medicaments from the receptacles during the aerosolizing process.
One promising way to deliver various drugs to a patient is by pulmonary delivery where a drug dispersion or aerosol is inhaled by the patient to permit the active drug within the dispersion to reach the distal or alveolar regions of the lung. Pulmonary drug delivery has shown to be particularly promising because certain drugs have been found to readily absorb within the blood circulation. For example, pulmonary delivery may be a useful approach for proteins and polypeptides that are difficult to deliver by other routes of administration.
A variety of techniques have been employed to deliver drugs to the lungs including liquid nebulizers, metered dose inhalers, and the like. Of particular interest to the invention are dry powder dispersion devices that are able to aerosolize powdered medicaments for inhalation by the patient. Exemplary apparatus for aerosolizing powdered medicaments are described in U.S. Pat. Nos. 5,458,135, 5,775,320, 5,740,794 and 5,785,049, and copending U.S. patent application Ser. No. 09/004,558, filed Jan. 8, 1998, Ser. No. 09/312,434, filed Jun. 4, 1999, No. 60/136,518, filed May 28, 1999, and No. 60/141,793, filed Jun. 30, 1999, the complete disclosures of which are herein incorporated by reference.
At least some of the apparatus described in the above references utilize a gas stream to draw the powder into an extraction tube where the powder is deagglomerated, entrained in the gas stream, and exits as an aerosol suitable for inhalation. In some cases, such apparatus may utilize a receptacle that has a penetrable lid. The extraction tube is inserted through the lid and a vent is also formed in the lid. The gas stream then draws air through the receptacle and into the extraction tube. The air drawn through the receptacle extracts the powder where it joins with the gas stream to form the aerosol. It is also possible to extract the powder from within a receptacle by use of a breath actuated device as described in U.S. patent application Ser. No. 60/141,793 cited above.
Hence, when utilizing such receptacles to hold the powder, a need exists for creating inlet and outlet openings in the receptacles to facilitate extraction of the powder. The manner in which these openings are created can be challenging. For example, it may be convenient to form such openings while the receptacle is within the aerosolizing apparatus. Due to the relatively small size of such apparatus, the proper formation of appropriately configured holes presents many technical challenges.
Further, in some cases, the openings may need to be precisely located and have a specified size. This can be especially challenging because of the wide variety of cavity shapes. Merely by way of example, copending U.S. patent application Ser. No. 60/172,317, filed Dec. 17, 1999, the complete disclosure of which is herein incorporated by reference, describes several shapes of cavities that may be used to hold a powder. Another challenging aspect may be the need to minimize the amount of material that is forced into the cavity during formation of the openings in order to increase the gas flow efficiency through the cavity.
Hence, the invention is related to techniques for forming openings in receptacles to maximize the efficiency with which the powder may be extracted and aerosolized.
In one embodiment, a method is provided for forming at least one opening in a receptacle that includes a cover with an exterior surface and an interior surface that covers a cavity. The cover is pierced with a blade of a cutting mechanism. The blade is then moved through the cover to cut a portion of the cover and create an opening in the cover to provide access into the cavity. As the blade is moved through the cover, the cut portion curls on top of the exterior surface so as to be outside of the cavity.
In one aspect, the cutting mechanism is rotated after the cover has been pierced to move the blade through the cover. Such a feature is advantageous in that a curved opening may be created in the cover. In another aspect, the cutting mechanism includes multiple blades so that multiple openings may be formed simultaneously when the cutting mechanism is rotated. In one specific aspect, the cutting mechanism may include three blades, and the cutting mechanism is rotated through an angle in the range from about 70 degrees to about 115 degrees to form three curved elongate openings in the cover. However, it will be appreciated that other numbers of blades may also be used.
In another particular aspect, the cutting mechanism comprises a support member, with the blade being angled in a forward direction relative to the support member by an angle in the range from about 50 degrees to about 80 degrees and more preferably from about 60 degrees to about 70 degrees. The blade is moved through the cover in the forward direction to permit the blade to direct the cut portion of the cover onto the exterior surface and away from the cavity. As the cut portion is removed, it rolls into a ball in one xe2x80x9cin tactxe2x80x9d piece that remains attached to the cover. In another particular aspect, the cavity has an outer periphery, and the opening is formed near or along the outer periphery. For example, at least a portion of the outer periphery may be curved. As the cutting mechanism is rotated, the opening that is produced is also curved and follows along the outer periphery.
In still another aspect, a central opening is formed in the cover while forming the elongate opening. Conveniently, a center cutting device may be employed to form the central opening while the elongate opening is also being formed. In this way, the cutting mechanism may be employed to simultaneously create inlet openings and an outlet opening to facilitate extraction of a powder from the cavity. Conveniently, the center cutting device may comprise a tubular member that extends from the support member. To form the central opening, the cover may be pierced with the blades of the center cutting device. The support member may then be rotated to form the central opening. One particular advantage of using the tubular member is that it may be used as a flow path when extracting the powder from the cavity. In one aspect, the outlet opening is formed first, followed by the outlet openings.
In another embodiment, a method is provided for aerosolizing a powder that is contained within a receptacle having a cover with an exterior surface and an interior surface covering a cavity that contains the powder. The method utilizes a cutting mechanism having at least one outer blade and a plurality of inner blades. According to the method, the cover is pierced with the outer blade and the inner blades, and the outer blade is moved through the cover to cut a portion of the cover and to create an elongate outer opening in the cover. As the outer opening is created, the cut portion curls on top of the exterior surface. Simultaneously, the inner blades are moved through the cover to cut an inner opening in the cover. Air is then drawn through the outer opening, through the cavity and out the inner opening to extract the powder from the receptacle and to aerosolize the powder.
In one particular aspect, the cutting mechanism comprises a support member from which the outer blade extends. The support member is maintained at a location that is spaced above the cover when cutting the openings and when extracting the powder. Such a configuration is convenient when the receptacle is opened within an aerosolizing apparatus where space may be limited. In one particular aspect, the outer opening has a width, B, and the support member is maintained at a location spaced apart from the cover by a distance, A, where A is greater than or equal to B. In still another aspect, the width, B, is in the range from about 0.3 mm to about 2 mm.
In still another aspect, a tubular member extends from the support member, with the inner blades being formed on the tubular member. As the support member is rotated, the inner blades on the tubular member form the inner opening. Conveniently, a gas stream may be flowed through at least a portion of the tubular member to draw the air through the cavity and out the tubular member. In this way, the same tubular member that is employed to form the inner opening may also be used in extracting the powder from the receptacle using a flowing gas stream.
In still another embodiment, a hole forming device is provided which comprises a support member and a plurality of outer blades extending downward from the support member at an angle in the range from about 50 degrees to about 80 degrees and more preferably from about 60 degrees to about 70 degrees. A tubular member extends downward from the support member, with the tubular member being surrounded by the outer blades. A distal end of the tubular member includes a plurality of inwardly directed and outwardly facing blades. With such a configuration, the hole forming device may be employed to form a plurality of outer openings and an inner opening as the blades are pierced through a cover and then rotated through the cover.
In one embodiment, an aerosolizing apparatus is provided which comprises a housing for holding a receptacle having a cover with an exterior surface and an interior surface covering a cavity that contains a powder. Disposed in the housing is a hole forming device for forming at least one inlet opening and an outlet opening in the cover. An aerosolizing system is also provided to extract powder from the receptacle by drawing air through the inlet opening, through the receptacle and out the outlet opening. The hole forming device comprises a support member having at least one outer blade that extends downward from the support member at an angle in the range from about 50 degrees to about 80 degrees and more preferably from about 60 degrees to about 70 degrees. The hole forming device also includes at least one inner blade. A moving mechanism is further provided to move the support member relative to the receptacle to move the outer blade through the cover and cause a cut portion of the cover to curl on top of the exterior surface to form the inlet opening, and to cut an outlet opening with the inner blade. Hence, with the aerosolizing apparatus, a receptacle may be placed into the housing and the hole forming device utilized to form an inlet opening and an outlet opening. The aerosolizing system may then be employed to extract the powder from the receptacle where it will be available for inhalation by a patient.
Conveniently, the hole forming device may include a plurality of outer blades for forming multiple inlet openings. Further, the hole forming device may include a tubular member that extends downward from the support member, with the distal end of the tubular member including a plurality of inwardly directed and outwardly facing inner blades. In this way, a gas stream may be flowed through at least a portion of the tubular member to draw gases through the inlet openings, through the cavity and through the tubular member to extract and aerosolize the powder. Conveniently, the gas stream may be produced by a gas source that is disposed within the housing. Alternatively, the aerosolizing apparatus may include a mouthpiece so that as the patient inhales from the mouthpiece, a gas stream is caused to flow through at least a portion of the tubular member to extract the powder.